Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a low cure rate and few therapeutic options. We recently discovered that approximately 50% of the pancreatic cancer cell lines tested in our lab (14 out of 31 lines) are highly sensitive to the selective BCL-XL inhibitor WEHI-539. Therefore, we will evaluate the potential efficacy of BCL-XL as a therapeutic target in PDAC both in vitro and in vivo. In addition, we will identify potential biomarkers of BCL-XL addiction, characterize mechanisms of sensitivity and resistance, and uncover novel drug combinations to further potentiate the activity of BCL-XL inhibitors in PDAC.